Preclinical pharmacology studies of antitumor agents under development of DTP are conducted under this contract to collect data which will be used to improve both the interpretation of preclinical toxicology data as well as the efficiency of the Phase I trials of new agents. Task Assignments are issued to contractors to perform defined pharmacologic projects. In general these studies are conducted in parallel with or prior to preclinical toxicology evaluations of the experimental agents. It is the expectation that from these studies will come assays of antitumor agents of sufficient sensitivity to be used in the clinic. Further studies will be designed to investigate the pharmacokinetics of the drug after bolus and infusion dosing in mice, rats and/or dogs. A major objective of this project is the collection of data which will ultimately lead to an understanding of species differences so that a significant reduction in the number of doses may result in the dose escalation schemes employed in Phase I clinical trials. The pharmacological information obtained through the Task Orders will play a potentially greater role in the drug development process in the future because of the increasing emphasis on in vitro screens which is contemplated in the next several years. Basic pharmacokinetic data will contribute to the planning of treatment regimens and when significant species differences are observed preclinically, the Phase I clinician is alerted to their potential human significance.